WO1994013287A1 - Use of 2-amino-6-a-propylamino-4,5,6,7-tetrahydrobenzothiazole (pramipexol) as an anti-depressant drug - Google Patents

Use of 2-amino-6-a-propylamino-4,5,6,7-tetrahydrobenzothiazole (pramipexol) as an anti-depressant drug Download PDF

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Publication number
WO1994013287A1
WO1994013287A1 PCT/EP1993/003389 EP9303389W WO9413287A1 WO 1994013287 A1 WO1994013287 A1 WO 1994013287A1 EP 9303389 W EP9303389 W EP 9303389W WO 9413287 A1 WO9413287 A1 WO 9413287A1
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Prior art keywords
amino
tetrahydrobenzothiazole
propyl
propylamino
snd
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PCT/EP1993/003389
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German (de)
French (fr)
Inventor
Rudolf Hammer
Joachim Mierau
Erich Lehr
Franco Borsini
Original Assignee
Boehringer Ingelheim Kg
Boehringer Ingelheim International Gmbh
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Priority to EP94902661A priority Critical patent/EP0675717B1/en
Application filed by Boehringer Ingelheim Kg, Boehringer Ingelheim International Gmbh filed Critical Boehringer Ingelheim Kg
Priority to DK94902661T priority patent/DK0675717T3/en
Priority to DE59309733T priority patent/DE59309733D1/en
Priority to KR1019950702272A priority patent/KR100311165B1/en
Priority to CA002150131A priority patent/CA2150131C/en
Priority to AU57152/94A priority patent/AU674378B2/en
Priority to PL93309282A priority patent/PL309282A1/en
Priority to UA95063059A priority patent/UA35604C2/en
Priority to JP51374394A priority patent/JP3221880B2/en
Priority to HU9501623A priority patent/HU221014B1/en
Priority to ES94902661T priority patent/ES2136725T3/en
Priority to SK740-95A priority patent/SK281441B6/en
Publication of WO1994013287A1 publication Critical patent/WO1994013287A1/en
Priority to NO952207A priority patent/NO306930B1/en
Priority to BG99700A priority patent/BG62475B1/en
Priority to FI952734A priority patent/FI952734A/en
Priority to HK98113329A priority patent/HK1019003A1/en
Priority to GR990402617T priority patent/GR3031521T3/en
Priority to US09/526,079 priority patent/US6191153B1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, ***e

Definitions

  • 100 mlg drip substance contain:
  • 1 suppository contains:
  • 1 ampoule contains:
  • the buffer substances, the active substance and sodium pyrosulfite are successively dissolved in boiled water and cooled under CO2 fumigation. Make up to the given volume with boiled water and filter without pyrogen,
  • 1 coated tablet contains:

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
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  • Medicinal Preparation (AREA)

Abstract

The invention concerns the use of pramipexol as an anti-depressant drug.

Description

Verwendung von 2-Am1no-6-A-propyl-amino-4,5,6,7-tetrahydrobenzoth1azo. (Pramipexol) als Arzneimittel mit antidepressiver WirkungUse of 2-Am1no-6-A-propyl-amino-4,5,6,7-tetrahydrobenzoth1azo. (Pramipexole) as a medicine with an antidepressant effect
Die vorliegende Erfindung betrifft die Verwendung von 2-Amino- 6-n-propyl-amino-4, 5,6, 7-tetrahydrobenzothiazol, insbesondere seines ( - ) -Enantiomeren, sowie deren pharmakologisch verträg¬ lichen Säureadditionssalze als Arzneimittel mit antidepressiver Wirkung.The present invention relates to the use of 2-amino-6-n-propylamino-4, 5,6, 7-tetrahydrobenzothiazole, in particular its (-) enantiomer, and their pharmacologically acceptable acid addition salts as medicaments with an antidepressant effect.
Die genannten Verbindungen sind als Arzneimittel bekannt, wobei die Behandlung der Schizophrenie und die Behandlung der parkinsonschen Krankheit im Vordergrund stehen. Einzelheiten zur Herstellung dieser Verbindungen - deren (-) -Enantiomeren in der Literatur auch als SND 919 oder Pramipexol bezeichnet wird, können der Europäischen Patentanmeldung EP-A 85 116 016 entnommen werden. Überraschenderweise wurde jetzt gefunden, daß Pramipexol antidepressive Eigenschaften aufweist. Von besonderer Bedeutung in diesem Zusammenhang ist, daß die Verbindung eine unerwartet geringe α-Rezeptor-Affinität besitzt und somit bei ausgezeichneter Verträglichkeit eine hohe selektive Wirkung hat. Die bislang nicht bekannte lange Wirkungsdauer (Halbwertszeit 12,5 Stunden) und eine unerwartet hohe Bioverfügbarkeit von über 80 % von Pramipexol erweisen sich als besonderer Vorteil bei der Verwendung als Antidepressivu .The compounds mentioned are known as medicaments, the treatment of schizophrenia and the treatment of Parkinson's disease being in the foreground. Details on the preparation of these compounds - whose (-) enantiomers are also referred to in the literature as SND 919 or pramipexole can be found in European patent application EP-A 85 116 016. Surprisingly, it has now been found that pramipexole has antidepressant properties. Of particular importance in this context is that the compound has an unexpectedly low α-receptor affinity and thus has a high selective effect with excellent tolerability. The previously unknown long duration of action (half-life 12.5 hours) and an unexpectedly high bioavailability of over 80% of pramipexole prove to be a particular advantage when used as an antidepressant.
Die antidepressive Wirkung von Pramipexol wurde in prae klinischen Untersuchungen im "forced swimming test" nachgewiesen. Einzelheiten dieses Verhaltenstests sind beispielsweise bei Willner, Psychopharmacology .83., -16 (1984) und Borsini und eli, Psychopharmacology S4_, 147 - 160 (1988) beschrieben. Pramipexol (SND 919) wurde gegenüber Amineptine - einem bekannten Antidepressivum - an acht Ratten untersucht. Beide Substanzen wurden in physiologischer Kochsalzlösung gelöst und parenteral verabreicht. Die Ergebnisse sind in der Tabelle 1 dargestellt.The antidepressant effect of pramipexole has been demonstrated in pre-clinical studies in the "forced swimming test". Details of this behavioral test are described, for example, in Willner, Psychopharmacology .83., -16 (1984) and Borsini and eli, Psychopharmacology S4_, 147-160 (1988). Pramipexole (SND 919) was tested against amineptine - a well-known antidepressant - in eight rats. Both substances were dissolved in physiological saline and administered parenterally. The results are shown in Table 1.
Tabelle 1: Untersuchungen von SND 919 und Amineptine im "forced swim ing test"Table 1: Investigations of SND 919 and amineptine in the "forced swim ing test"
Verbindung Dosis Immobilitatszeit mg/kg (Sek.)Compound dose immobilization time mg / kg (sec.)
Salzlösung SND 919 SND 919 SND 919 Amineptine
Figure imgf000004_0001
Saline solution SND 919 SND 919 SND 919 amineptine
Figure imgf000004_0001
Die vorliegenden Ergebnisse belegen eine deutliche Überlegenheit von SND 919 gegenüber Amineptine.The present results show that SND 919 is clearly superior to amineptine.
Pramipexol kann zur Behandlung von Depressionen in Form üblicher galenischer Zubereitungen angewendet werden, die im wesentlichen aus einem inerten pharmazeutischen Träger und einer effektiven Dosis des Wirkstoffes bestehen, wie z.B. Tabletten, Dragees, Kapseln, Oblaten, Pulver, Lösungen, Suspensionen, Emulsionen, Sirupe, Suppositorien usw.. Eine therapeutisch wirksame Einzeldosis der erfindungsgemäß gefundenen Indikation liegt im Bereich zwischen 0,1 und 30 mg, bevorzugt zwischen 1 und 5 mg. Neben einer oralen oder intravenösen Applikation kann Pramipexol auch transdermal angewendet werden. Geeignete Freigabesysteme hierzu sind aus dem Stand der Technik bekannt, beispielsweise aus der Europäischen Patentanmeldung 428 038.Pramipexole can be used to treat depression in the form of conventional pharmaceutical preparations which essentially consist of an inert pharmaceutical carrier and an effective dose of the active ingredient, such as tablets, coated tablets, capsules, wafers, powders, solutions, suspensions, emulsions, syrups, Suppositories, etc. A therapeutically effective single dose of the indication found according to the invention is in the range between 0.1 and 30 mg, preferably between 1 and 5 mg. In addition to oral or intravenous administration, pramipexole can also be used transdermally. Suitable release systems for this are from known in the art, for example from European patent application 428 038.
Beispiel 1example 1
Drageekern mit 5 mg 2-Amino-6-n-propyl-amino-4.5.6.7- tetrahydro-benzthiazol-dihydrochloridCoated tablets with 5 mg of 2-amino-6-n-propyl-amino-4.5.6.7-tetrahydro-benzothiazole-dihydrochloride
Zusammensetzung:Composition:
1 Drageekern enthält:1 coated tablet contains:
SND 919 5,0 mgSND 919 5.0 mg
Milchzucker 33,5 mgMilk sugar 33.5 mg
Maisstärke 10,0 mgCorn starch 10.0 mg
Gelatine 1,0 mgGelatin 1.0 mg
Magnesiumstearat 0, 5 mgMagnesium stearate 0.5 mg
50,0 mg50.0 mg
Herstellungsverfahrenproduction method
Die Mischung der Wirksubstanz mit Milchzucker und Maisstärke wird mit einer 10 %igen wassrigen Gelatinelösung durch ein Sieb von 1 mm Maschenweite granuliert, bei 40 C getrocknet und nochmals durch obiges Sieb gerieben. Das so erhaltene Granulat wird mit Magnesiumstearat gemischt und zu Drageekernen verpreßt. Die Herstellung muß in abgedunkelten Räumen vorgenommen werden.The mixture of the active substance with milk sugar and corn starch is granulated with a 10% aqueous gelatin solution through a sieve with a mesh size of 1 mm, dried at 40 ° C. and rubbed again through the above sieve. The granules obtained in this way are mixed with magnesium stearate and pressed to dragee cores. The production must be carried out in darkened rooms.
Kerngewicht: 50 mgCore weight: 50 mg
Stempel: 5 mm, gewölbtStamp: 5 mm, domed
Die so erhaltenen Drageekerne werden nach bekanntem Verfahren mit einer Hülle überzogen, die im wesentlichen aus Zucker und Talkum besteht. Die fertigen Dragees werden mit Hilfe von Bienenwachs poliert.The dragee cores obtained in this way are coated according to a known method with an envelope consisting essentially of sugar and Talc exists. The finished coated tablets are polished with the help of beeswax.
Drageegewicht: 100 mgDrage weight: 100 mg
Beispiel 2Example 2
Tropfen mit 5 mg 2-Amino-6-n-propyl-amino-4,5.6,7- tetrahydro-benzthiazol-dihydrochloridDrop with 5 mg of 2-amino-6-n-propyl-amino-4,5,6,7-tetrahydro-benzothiazole-dihydrochloride
Zusammensetzung:Composition:
100 mlg TropfSubstanz enthalten:100 mlg drip substance contain:
p-Hydroxybenzoesäure-methylester p-Hydroxybenzoesäure-n-propylesterp-Hydroxybenzoic acid methyl ester p-hydroxybenzoic acid n-propyl ester
AnisölAnise oil
Mentholmenthol
Ethanol reinPure ethanol
SND 919SND 919
Zitronensäurecitric acid
Natriumphosphat sek. x 2H2OSodium phosphate sec. x 2H 2 O
NatriumcyclamatSodium cyclamate
GlycerinGlycerin
Dest. Wasser
Figure imgf000006_0001
Dest. Water
Figure imgf000006_0001
Herstellungsverfahren:Production method:
Die p-Hydroxybenzoesäureester, Anisöl sowie Menthol werden in Ethanol gelöst (Lösung I) . Die Puffersubstanzen, die Wirksubstanz und Natriumcyclamat werden in dest. Wasser gelöst Glycerin zugefügt (Lösung II) . Lösung I wird in Lösung II eingerührt und die Mischung mit dest. Wasser auf das gegebene Volumen aufgefüllt. Die fertige Tropflδsung wird durch ein geeignetes Filter filtriert. Die Herstellung und Abfüllung der Tropflδsung muß unter Lichtschutz und unter Schutzbegasung erfolgen.The p-hydroxybenzoic acid esters, anise oil and menthol are dissolved in ethanol (solution I). The buffer substances, the active substance and sodium cyclamate are in dist. Water dissolved glycerin added (solution II). Solution I is stirred into solution II and the mixture with dist. Make up water to the given volume. The finished drip solution is replaced by a suitable filter filtered. The production and filling of the drip solution must take place under light protection and with protective gassing.
Beispiel 3Example 3
Suppositotiren mit 10 mg 2-Amino-6-n-propyl-amino-4,5, 6.7- tetrahydro-benzthiazol-dihydrochloridSuppositotiren with 10 mg 2-amino-6-n-propyl-amino-4,5, 6.7-tetrahydro-benzothiazole-dihydrochloride
1 Zäpfchen enthält:1 suppository contains:
SND 919 10,0 mgSND 919 10.0 mg
Zäpfchenmassen (z.B. Witepsol W 45) 1690,0 mgSuppository masses (e.g. Witepsol W 45) 1690.0 mg
1700,0 mg1700.0 mg
Herstellungsverfahren:Production method:
Die feingepulverte Substanz wird mit Hilfe eines Eintauchhomogenisators in die geschmolzene und auf 40°C abgekühlte Zäpfchenmassen eingerührt. Die Masse sind bei 35°C in leicht vorgekühlte Formen ausgegossen.The finely powdered substance is stirred into the molten suppository mass, which has been cooled to 40 ° C., using an immersion homogenizer. The masses are poured into slightly pre-cooled molds at 35 ° C.
Zäpfchengewicht: 1,7 g Suppository weight: 1.7 g
Beispiel 4Example 4
Ampullen mit 5 mg 2-Amino-6-n-propyl-amino-4.5, 6,7- tetrahydro-benzthiazol-dihydrochloridAmpoules with 5 mg of 2-amino-6-n-propyl-amino-4.5, 6,7-tetrahydro-benzothiazole dihydrochloride
1 Ampulle enthält:1 ampoule contains:
SND 919 5, 0 mgSND 919 5.0 mg
Zitronensäure 7,0 mgCitric acid 7.0 mg
Natriumphosphat sek. x 2H2O 3,0 mgSodium phosphate sec. x 2H2O 3.0 mg
Natriumpyrosulfit 1,0 mgSodium pyrosulfite 1.0 mg
Dest. Wasser ad 1,0 mlDest. Water ad 1.0 ml
Herstellungsverfahren:Production method:
In ausgekochtem und unter CO2-Begasung abgekühltem Wasser werden nacheinander die Puffersubstanzen, die Wirksubstanz sowie Natriumpyrosulfit gelöst. Man füllt mit abgekochtem Wasser auf das gegebene Volumen auf und filtriert pyrogenfrei,The buffer substances, the active substance and sodium pyrosulfite are successively dissolved in boiled water and cooled under CO2 fumigation. Make up to the given volume with boiled water and filter without pyrogen,
Abfüllung: in braune Ampullen unterBottling: in brown ampoules under
SchutzbegasungProtective fumigation
Sterilisation: 20 Minuten bei 120°CSterilization: 20 minutes at 120 ° C
Die Herstellung und Abfüllung der Ampullenlösung muß in abgedunkelten Räumen vorgenommen werden. Beispiel 5The preparation and filling of the ampoule solution must be carried out in darkened rooms. Example 5
Dragees mit 10 mg 2-Amino-6-n-propyl-amino-4.5.6.7-tetrahydro- benzthiazol-dihydrochloridCoated tablets with 10 mg of 2-amino-6-n-propyl-amino-4.5.6.7-tetrahydrobenzthiazole dihydrochloride
1 Drageekern enthält:1 coated tablet contains:
SND 919 10,0 mgSND 919 10.0 mg
Milchzucker 35,5 mgMilk sugar 35.5 mg
Maisstärke 12,0 mgCorn starch 12.0 mg
Gelatine 1,0 mgGelatin 1.0 mg
Magenesiumstearat 0,5 mgGastric esium stearate 0.5 mg
59 mg59 mg
Herstellungsverfahren: Analog Beispiel 1. Production process: Analogous to example 1.

Claims

PatentansprücheClaims
1) Verwendung von 2-Amino-6-n-propyl-amino-4, 5, 6, 7- tetrahydrobenzothiazol sowie seiner pharmakologisch verträglichen Saureadditionssalze zur Behandlung von Depressionen.1) Use of 2-amino-6-n-propyl-amino-4, 5, 6, 7-tetrahydrobenzothiazole and its pharmacologically acceptable acid addition salts for the treatment of depression.
2) Verwendung von (- ) -2-Amino-6-n-propyl-amino- 4, 5, 6, 7-tetrahydrobenzthiazol sowie seiner pharmakologisch verträglichen Saureadditionssalze als Arzneimittel mit antidepressiver Wirkung.2) Use of (-) -2-amino-6-n-propyl-amino-4, 5, 6, 7-tetrahydrobenzthiazole and its pharmacologically acceptable acid addition salts as medicaments with an antidepressant effect.
3) Verwendung von 2-Amino-6-n-propyl-amino-4,5, 6, 7- tetrahydrobenzothiazol sowie seiner pharmakologisch verträglichen Saureadditionssalze zur Herstellung eines Arzneimittels zur Behandlung von Depressionen.3) Use of 2-amino-6-n-propyl-amino-4,5, 6, 7-tetrahydrobenzothiazole and its pharmacologically acceptable acid addition salts for the manufacture of a medicament for the treatment of depression.
4) Verwendung von (-) -2-Amino-6-n-propyl-amino- 4,5, 6, 7-tetrahydrobenzothiazol sowie seiner pharmakologisch verträglichen Saureadditionssalze zur Herstellung eines Arzneimittels zur Behandlung von Depressionen.4) Use of (-) -2-amino-6-n-propyl-amino-4,5, 6, 7-tetrahydrobenzothiazole and its pharmacologically acceptable acid addition salts for the manufacture of a medicament for the treatment of depression.
5) Verwendung von 2-Amino-6-n-propyl-amino-5) Use of 2-amino-6-n-propylamino
4,5, 6, 7-tetrahydrobenzthiazol sowie seiner pharmakologisch verträglichen Saureadditionssalze als Arzneimittel mit antidepressiver Wirkung. 4,5, 6, 7-tetrahydrobenzthiazole and its pharmacologically acceptable acid addition salts as medicines with antidepressant effects.
PCT/EP1993/003389 1992-12-05 1993-12-02 Use of 2-amino-6-a-propylamino-4,5,6,7-tetrahydrobenzothiazole (pramipexol) as an anti-depressant drug WO1994013287A1 (en)

Priority Applications (18)

Application Number Priority Date Filing Date Title
UA95063059A UA35604C2 (en) 1992-12-05 1993-12-02 Pharmaceutical composition possessing antidepressant activity
DK94902661T DK0675717T3 (en) 1992-12-05 1993-12-02 Use of 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole (pramipexole) as a drug with antidepressant effect
DE59309733T DE59309733D1 (en) 1992-12-05 1993-12-02 USE OF 2-AMINO-6-A-PROPYL-AMINO-4,5,6,7-TETRAHYDROBENZOTHIAZOLE (PRAMIPEXOL) AS A MEDICINAL PRODUCT WITH ANTIDEPRESSIVE EFFECT
KR1019950702272A KR100311165B1 (en) 1992-12-05 1993-12-02 Pharmaceutical composition for treating depression containing pramifelsol
CA002150131A CA2150131C (en) 1992-12-05 1993-12-02 Use of 2-amino-6-n-propyl-amino-4,5,6,7-tetrahydrobenzothiazole as a pharmaceutical composition having an antidepressant activity
AU57152/94A AU674378B2 (en) 1992-12-05 1993-12-02 Use of 2-amino-6-A-propylamino-4,5,6, 7-tetrahydrobenzothiazole (pramipexol) as an anti-depressantdrug
HU9501623A HU221014B1 (en) 1992-12-05 1993-12-02 Process for preparing pharmaceutical compositions of antidepressant use of 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole in the production of a medicament for the treatment of depression
JP51374394A JP3221880B2 (en) 1992-12-05 1993-12-02 Use of 2-amino-6-n-propyl-amino-4,5,6,7-tetrahydrobenzothiazole as a pharmaceutical composition with antidepressant action
PL93309282A PL309282A1 (en) 1992-12-05 1993-12-02 Application of 2-amino-6-n-propyl-amino- 4,5,6,7-tetrahydrobenzothiasole (pramipexol) as an antidepressant
EP94902661A EP0675717B1 (en) 1992-12-05 1993-12-02 Use of 2-amino-6-a-propylamino-4,5,6,7-tetrahydrobenzothiazole (pramipexol) as an anti-depressant drug
ES94902661T ES2136725T3 (en) 1992-12-05 1993-12-02 USE OF 2-AMINO-6-N-PROPIL-AMINO-4,5,6,7-TETRAHIDROBENZOTIAZOLE (PRAMIPEXOL) AS AN ANTIDEPRESSIVE EFFECT MEDICATION.
SK740-95A SK281441B6 (en) 1992-12-05 1993-12-02 Use of 2-amino-6-a-propylamino-4,5,6,7-tetrahydrobenzothiazole
NO952207A NO306930B1 (en) 1992-12-05 1995-06-02 Use of 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole (Pramipexole) as an antidepressant
FI952734A FI952734A (en) 1992-12-05 1995-06-05 The use of 2-amino-6-A-propylamino-4,5,6,7-tetrahydrobenzothiazole (Pramipexole) as a drug with antidepressant effect
BG99700A BG62475B1 (en) 1992-12-05 1995-06-05 Application of 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole for the treatment of depression
HK98113329A HK1019003A1 (en) 1992-12-05 1998-12-14 Use of 2-amino-6-a-propylamino-4,5,6,7- tetrahydrobenzothiazole(pram ipexol) as an anti-depressant drug
GR990402617T GR3031521T3 (en) 1992-12-05 1999-10-13 Use of 2-amino-6-a-propylamino-4,5,6,7-tetrahydrobenzothiazole (pramipexol) as an anti-depressant drug.
US09/526,079 US6191153B1 (en) 1992-12-05 2000-03-15 Use of 2-amino-6-n-propyl-amino-4,5,6,7-tetrahydrobenzothiazole as a pharmaceutical composition having an antidepressant activity

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE4241013A DE4241013A1 (en) 1992-12-05 1992-12-05 Use of 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole as antidepressant drug
DEP4241013.4 1992-12-05

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CN (1) CN1052400C (en)
AT (1) ATE183091T1 (en)
AU (1) AU674378B2 (en)
BG (1) BG62475B1 (en)
CA (1) CA2150131C (en)
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DE (2) DE4241013A1 (en)
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ES (1) ES2136725T3 (en)
FI (1) FI952734A (en)
GR (1) GR3031521T3 (en)
HK (1) HK1019003A1 (en)
HU (1) HU221014B1 (en)
IL (1) IL107870A (en)
MX (1) MX9307644A (en)
NO (1) NO306930B1 (en)
NZ (1) NZ258876A (en)
PL (1) PL309282A1 (en)
RU (1) RU2157685C2 (en)
SG (1) SG49228A1 (en)
SK (1) SK281441B6 (en)
TW (1) TW362973B (en)
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WO (1) WO1994013287A1 (en)
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5650420A (en) * 1994-12-15 1997-07-22 Pharmacia & Upjohn Company Pramipexole as a neuroprotective agent
US6001861A (en) * 1998-01-16 1999-12-14 Pharmacia & Upjohn Company Use of pramipexole in the treatment of restless legs syndrome
WO2000006162A1 (en) * 1998-07-27 2000-02-10 Boehringer Ingelheim Pharma Kg Agents with antidepressant action, containing pramipexol and a further antidepressant
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US6458820B1 (en) 1994-12-15 2002-10-01 Pharmacia & Upjohn Company Method for preventing or the progression of neuronal damage with pramipexole as a neuroprotective agent
US5650420A (en) * 1994-12-15 1997-07-22 Pharmacia & Upjohn Company Pramipexole as a neuroprotective agent
US6194445B1 (en) 1997-01-17 2001-02-27 Pharmacia & Upjohn Company Use of pramipexole in the treatment of restless legs syndrome
US6001861A (en) * 1998-01-16 1999-12-14 Pharmacia & Upjohn Company Use of pramipexole in the treatment of restless legs syndrome
WO2000002542A3 (en) * 1998-07-07 2000-06-22 Boehringer Ingelheim Pharma Agents with an antidepressive effect containing pramipexol and an additional antidepressant drug
BG64972B1 (en) * 1998-07-07 2006-11-30 Boehringer Ingelheim Pharma Kg Agents with antidepressive effect
WO2000006162A1 (en) * 1998-07-27 2000-02-10 Boehringer Ingelheim Pharma Kg Agents with antidepressant action, containing pramipexol and a further antidepressant
US6410579B2 (en) 2000-02-23 2002-06-25 Pharmacia & Upjohn Company Use of pramipexole for the treatment of addictive disorders
EP1260221A2 (en) * 2001-05-23 2002-11-27 Pfizer Products Inc. Combination treatment for depression and anxiety
KR20020090152A (en) * 2001-05-23 2002-11-30 화이자 프로덕츠 인크. Combination treatment for depression and anxiety
EP1260221A3 (en) * 2001-05-23 2002-12-18 Pfizer Products Inc. Combination treatment for depression and anxiety
DE102004006808A1 (en) * 2004-02-11 2005-09-01 Grünenthal GmbH Substituted 4,5,6,7-tetrahydro-benzothiazol-2-ylamine compounds
US7348347B2 (en) 2004-02-11 2008-03-25 Gruenenthal Gmbh Substituted 4,5,6,7-tetrahydrobenzthiazol-2-ylamine compounds

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